Understanding the role of neuromodulators for cortical function requires the study of their effects at the level of neural responses, as well as at the level of behavioral responses. Theoretical models of olfactory processing, supported by behavioral lesion experiments, predict that cholinergic modulation in the olfactory system would serve to increase the discrimination between similar olfactory stimuli. In vivo extracellular recording techniques will be employed in this research project to test how the olfactory responses of cells in the olfactory bulb and cortex are modulated by cholinergic inputs. The molecular response spectra of mitral cells in the olfactory bulb and of pyramidal cells in the olfactory cortex are modulated by cholinergic inputs in such a way as to increase the discrimination of similar odorants by these cells. Extracellular recording techniques will be used in the olfactory bulb and cortex of anesthetized rats to analyze the degree of overlap in neural activity patterns in response to series of n-aliphatic aldehydes and n-fatty acids. Electrical stimulation of the horizontal limb of the diagonal band of Broca will be used to activate cholinergic projections to the olfactory bulb and cortex. The comparison of neural response profiles to odorants in the absence and in the presence of the stimulation of cholinergic fibers will serve to determine how changes in cholinergic modulation affect odor responses. The cholinergic nature of the observed effects will be tested by injection of cholinergic antagonists (muscarinic and/or nicotinic). The results from these experiments will help understand the processes underlying impairments in odor processing and learning observed in behavioral studies and will test predictions about the functional role of cholinergic modulation in sensory processing.